PURPOSE To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS). PATIENTS AND METHODS CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria. RESULTS Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature. CONCLUSION Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

With the increasing number of poorly water-soluble compounds in drug discovery pipelines, supersaturating drug delivery systems (SDDS) have attracted increased attention as an effective bioavailability enhancing approach. However, a systematic and quantitative synopsis of the knowledge about performance of SDDS is currently lacking. Such analysis of the recent achievements is to provide insights for formulation scientists dealing with poorly soluble compounds. Areas covered: A systematic search of two evidence-based International databases, Medline and Embase, from 2010 to Dec 2015, has been performed. By conducting meta-analysis, box-plots, and correlation plots of the relevant data retrieved from literature, the current review addresses three quantitative questions: (1) how promising are SDDS for bioavailability enhancement? (2) which types of SDDS perform best? and (3) what are the most promising drug candidates? Four widely reported types of SDDS were compared: amorphous solid dispersions, nano-drug systems, supersaturable lipid-based formulations, and silica-based systems. Expert opinion: While SDDS formulations appear to be a promising candidate-enabling technique for drug development, the prediction of their in vivo performance by in vitro testing remains challenging. A transition from a trial-and-error development approach towards an approach guided by mechanistic insight, as well as the development of more efficient predictive tools for performance ranking is urgently needed.

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